Inflammation plays a fundamental role in host defenses and the progression of immune-mediated diseases. The inflammatory response is initiated in response to tissue injury (e.g., trauma, ischemia, and foreign particles) and infection by a complex cascade of events, including chemical mediators (e.g., cytokines and prostaglandins) and inflammatory cells (e.g., leukocytes). The inflammatory response is characterized by increased blood flow, increased capillary permeability, and the influx of phagocytic cells. These events result in swelling, redness, warmth (altered heat patterns), and pus formation at the site of injury.
A delicate well-balanced interplay between the humoral and cellular immune elements in the inflammatory response enables the elimination of harmful agents and the initiation of the repair of damaged tissue. When this delicately balanced interplay is disrupted, the inflammatory response may result in considerable damage to normal tissue of uncontrolled inflammatory responses, clinical intervention is needed to prevent tissue damage and organ dysfunction. Diseases such as Rheumatoid Arthritis, Osteoarthritis, Crohn's disease, psoriasis, or inflammatory bowel disease, are characterized by chronic inflammation.
Early detection and localization of inflammation is a critical step in the implementation of appropriate treatment of a subject. However, non-invasive techniques for the detection of inflammation remain elusive. A variety of techniques including computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and scintigraphic imaging are used to attempt to image secondary effects of markers of inflammation. However, CT, MRI, and ultrasonography rely on anatomical changes that result from inflammation, which occur late in the inflammatory response (van der Laken, C. J., et al., 1998, European Journal of Nuclear Medicine 25: 535-546). Therefore, these techniques are not useful for detecting the early phase in the development of inflammation. Scintigraphic imaging is a non-invasive method of scanning the entire body using radiopharmaceuticals (e.g., radiolabeled receptor-specific small proteins and peptides), which specifically bind to receptors abundant in the area of inflammation. The use of radiopharmaceuticals for imaging inflammation is limiting because it requires: (i) that the radiopharmaceutical specifically interacts with its receptor; (ii) that the radiopharmaceutical has a high affinity for its receptor; (iii) that the radiopharmaceutical specifically localizes to the site of inflammation, which is dependent on the receptor expression in the inflammatory response; (iv) that the receptor is accessible to the radiopharmaceutical; (v) that the radiopharmaceutical has high and early uptake; (vi) that the radiopharmaceutical is rapidly cleared; (vii) that the radiopharmaceutical does not accumulate in non-targeted tissues and result in high background; and (viii) that the radiopharmaceutical is not toxic (van der Laken, C. J., et al., 1998, European Journal of Nuclear Medicine 25: 535-546). The induction of a biological response by a radiopharmaceutical is a major drawback of using scintigraphic imaging. In addition to these technologies, inflammation may also be detected by feeling or visual observance of the site of injury or pain. However, this method is only useful for detecting the late stages in the development of inflammation.
The inability to diagnose and image inflammation in vivo continues to be a major obstacle to the successful treatment of inflammatory disorders. Currently, the only viable method for diagnosing inflammatory disorders, such as fibrosis, is by biopsy. This method is invasive and often results in an amount of healthy tissue being removed along with the tissue suspected of being affected by inflammation. Therefore, a great need exists for an accurate, non-invasive, rapid, and inexpensive method for detecting inflammation.